The overall objective of this contract is to evaluate vaccine prophylaxis against infectious diseases in infants and children. While the incidence, morbidity and mortality due to bacterial infection has significantly decreased in the developed world due to improvements in sanitation, the introduction of antibiotic therapy, and active immunization with bacterial vaccines, bacterial infections are still responsible for the deaths of many children in developing countries. Even in the U.S., bacteria including B. pertussis, H. influenzae type b, non-typable H. influenzae strains, S. pneumoniae, N. meningitidis, and several enteric organisms, cause disease, mortality and morbidity in significant numbers of children annually. New vaccine candidates continue to be developed, nurtured by basic research advances. These include several effective, nontoxic acellular vaccines against pertussis to replace the conventional whole cell vaccine, and polysaccharide- protein conjugate vaccines against H. influenzae, N. meningitidis, and S. pneumoniae. The development of a multivalent one dose immunogenic vaccine for delivery to young infants prior to disease exposure is a long-term goal of the Children's Vaccine Initiative, and the dedicated Pediatric Vaccine Evaluation Unit (PVEU) is expected to facilitate this development. As the number of safe and effective vaccines increases, thoughtful yet innovative strategies for multiple delivery systems and alternative delivery systems become necessary. These include the admixture of some of the polysaccharide-protein conjugate vaccines, or the simultaneous administration of these vaccines. These strategies require exploration of issues such as practicality, clinical acceptability, competitive antigenicity, immunogenicity, and adverse effects. The work in this contract encompasses Phase I and Phase II clinical trials of candidate vaccines of various types.